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A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells
Published on: March 28, 2021
Next-generation sequencing (NGS) analysis and age-based survival comparison among glioblastoma (GBM) patients: a
Chul Ou Lee1, Sun Yong Park2, Yejin Yun2
1Department of Neurosurgery, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
Objective:
Glioblastoma (GBM) incidence increases with age, and its etiologies may differ between young and elderly patients. This study aimed to investigate genetic differences between young and elderly GBM patients using next-generation sequencing (NGS) data.
Methods:
We retrospectively analyzed 124 GBM patients (< 65 years, n = 60; ≥ 65 years, n = 64) who underwent surgery at two institutions between 2017 and 2022. Clinical and NGS molecular data were analyzed, and survival analysis used the Kaplan-Meier method and Cox regression models.
Results:
The elderly group (≥ 65 years) had a significantly lower OS of 11.0 months compared to 18.0 months in the younger group (p = 0.001). The Stupp protocol, a known prognostic factor, was more frequent in the younger group (p = 0.023). Molecular analysis showed that MGMT methylation was more prevalent in elderly patients than in younger patients (p = 0.009). NGS genetic results showed that ATRX mutations were more common in younger patients than in elderly patients (p = 0.052, Fisher's exact test) but this was not statistically significant. Trends toward higher MET and CDK6 amplification rates were observed in the elderly group compared to the younger group (p = 0.058, Fisher's exact test), although these did not reach statistical significance. Multivariate analysis confirmed that advanced age (HR = 1.961, p = 0.002), MGMT methylation (HR = 0.513, p = 0.004), the Stupp protocol (HR = 0.376, p < 0.001), and GTR (HR = 0.519, p = 0.002) were independent prognostic factors.
Conclusion:
MGMT methylation was significantly more prevalent in elderly GBM patients and favorably influenced prognosis. No NGS-derived genetic alterations reached statistical significance between age groups after Fisher's exact test and multiple testing correction. Larger multicenter studies are needed to validate these exploratory findings.
